What did CRISPR-Cas9 accomplish in its first 10 years?

It’s been 10 years now from the debut of clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) era in which gene engineering has never been so accessible, precise and efficient. This technology, like a refined surgical procedure, has offered the ability of removing different types of disease causing mutations and restoring key proteins activity with ease of outperforming the previous resembling methods: zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs). Additionally, CRISPR-Cas9 systems can systematically introduce genetic sequences to the specific sites in the human genome allowing to stimulate desired functions such as anti-tumoral and anti-infectious faculties. The present brief review provides an updated resume of CRISPR-Cas9’s top achievements from its first appearance to the current date focusing on the breakthrough research including in vitro, in vivo and human studies. This enables the evaluation of the previous phase ‘the proof-of-concept phase’ and marks the beginning of the next phase which will probably bring a spate of clinical trials

Glomus tumor of the foot dorsum: A case report of a neglect podiatric entity

Key Clinical Message Podiatrists and orthopedists should be vigilant for chronically evolving, hyperalgic soft lumps in the foot with vascular radiological features, prompting early detection of glomus tumor, timely mass removal, providing pain relief and improving patient's quality of life. Abstract Glomus tumors refers to a rare group of benign perivascular neoplasms that originate from a neuromyoarterial structure called a glomus body. These tumors are characterized by their painful nature and predominant distribution in the extremities mainly the fingers, the hands and the feet. Nonetheless, the diagnosis is usually made after several years of symptoms experience as the lesions are mostly small, not palpable, and have variable presentations. Radiological workup especially with magnetic resonance imaging is very useful for diagnosing the tumoral process, however, confirmation can only be obtained by histological analysis. The treatment is purely surgical, and it is successful in most cases. Herein, we describe a case of glomus tumor of the foot dorsal side among a middle age male patient

The efficacy and safety of difelikefalin for pruritus in hemodialysis patients: a systematic review and meta-analysis of randomized controlled trials

Background Chronic kidney disease–associated pruritus (CKD-ap) is a common complication that negatively affects the quality of life. Difelikefalin has emerged as a novel FDA-approved drug to manage CKD-ap. This systematic review and meta-analysis will assess the efficacy and safety of Difelikefalin versus placebo to manage CKD-ap.Methods PubMed, Scopus, WOS, Central, and Embase were systematically searched until November 2023. RevMan was used to perform meta-analysis. Quality assessment was conducted using the Cochrane RoB 2.0 tool. Results were reported as risk ratio (RR) and mean difference (MD) with a 95% confidence interval (CI). PROSPERO ID: (CRD42023485979).Results Five RCTs with a total of 896 participants were included. Difelikefalin significantly decreased the weekly mean WI-NRS score (MD: −0.99 [−1.22, −0.75], p ˂ .00001), 5-D itch scale total score (MD: −1.51 [−2.26, −0.76], p > .0001), and Skindex-10 total score (MD: −7.39 [−12.51, −2.28], p = .005), but showed significantly higher adverse events (RR: 1.26 [1.03, 1.55], p = .03), versus placebo. However, there was no significant difference between both groups in serious adverse events (RR: 1.42 [0.78, 2.57], p = .25) or death (RR: 0.81 [0.19, 3.34], p = .77).Conclusion Difelikefalin appears to be a promising agent for the management of CKD-induced pruritus in patients with end-stage renal disease. However, evidence is still underpowered due to the paucity of the current data; therefore, more robust RCTs are required to confirm the benefit of Difelikefalin

The efficacy and safety of exercise regimens to mitigate chemotherapy cardiotoxicity: a systematic review and meta-analysis of randomized controlled trials

Abstract Background Cardiotoxicity is one of the most common adverse events of the chemotherapy. Physical exercise was shown to be cardioprotective. We aim to estimate the efficacy and safety of exercise in cancer patients receiving cardiotoxic chemotherapy. Methods We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, SCOPUS, Cochrane, Clinical Trials.gov, and MedRxiv through July 17th, 2023. We used RevMan V. 5.4 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI). PROSPERO ID: CRD42023460902. Results We included thirteen RCTs with a total of 952 patients. Exercise significantly increased VO2 peak (MD: 1.95 with 95% CI [0.59, 3.32], P = 0.005). However, there was no significant effect regarding left ventricular ejection fraction, global longitudinal strain, cardiac output, stroke volume, left ventricular end-diastolic volume, left ventricular end-systolic volume, E/A ratio, resting heart rate, peak heart rate, resting systolic blood pressure, and resting diastolic blood pressure. Also, there was no significant difference regarding any adverse events (AEs) (RR: 4.44 with 95% CI [0.47, 41.56], P = 0.19), AEs leading to withdrawal (RR: 2.87 with 95% CI [0.79, 10.43], P = 0.11), serious AEs (RR: 3.00 with 95% CI [0.14, 65.90], P = 0.49), or all-cause mortality (RR: 0.25 with 95% CI [0.03, 2.22], P = 0.21). Conclusion Exercise is associated with increased VO2 peak in cancer patients receiving cardiotoxic chemotherapy. However, there was no significant difference between exercise and usual care regarding the echocardiographic and safety outcomes